Complex structures obtained from dissolving-droplet nanoparticle assembly

ABSTRACT

Some variations provide an interspersed assembly of nanoparticles, the assembly comprising a first phase containing first nanoparticles and a second phase containing second nanoparticles, wherein the second phase is interspersed with the first phase, and wherein the first nanoparticles are compositionally different than the second nanoparticles. The interspersed assembly may be a semi-ordered assembly comprising discrete first-phase particles surrounded by a continuous second phase. Other variations provide a core-shell assembly of nanoparticles, the assembly comprising a first phase containing first nanoparticles and a second phase containing compositionally distinct second nanoparticles, wherein the second phase forms a shell surrounding a core of the first phase. The disclosed assemblies may have a volume from 1 μm 3  to 1 mm 3 , a packing fraction from 20% to 100%, and an average relative surface roughness less than 5%, for example. Methods of making these assemblies are described, and many experimental examples are included.

PRIORITY DATA

This patent application is a continuation-in-part application of U.S.patent application Ser. Nos. 16/411,058 and 16/411,061, each filed onMay 13, 2019, which are hereby incorporated by reference herein. Thispatent application also claims priority to U.S. Provisional Patent App.No. 62/953,635, filed on Dec. 26, 2019, which is hereby incorporated byreference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with Government support under DARPA Contract No.FA8650-15-C-7549. The Government has certain rights in this invention.

FIELD OF THE INVENTION

The present invention generally relates to assemblies of particles andmethods for assembling particles.

BACKGROUND OF THE INVENTION

Tightly packed, organic-free arrays of nanoparticles are useful foroptical, magnetic, electronic device, and pharmaceutical applications,among others. Applications include drive motors, windshield wipermotors, starter motors, pumps, and actuation devices. The macroscopicassembly of magnetic nanoparticles is useful for such magnetic devices.

Furthermore, assemblies of nanoparticles are useful for altering thewetting and icing on surfaces as well as for creating opticallyscattering or diffractive coatings, useful for cameras or thermalcontrol coatings, for example.

Micron-sized lenses, prisms, and retroreflectors are useful forchip-scale infrared and visible optics. There is no way to grind lensmaterials down to 10 micron sizes, for example.

There are existing approaches for forming packed nanoparticles, but theydo not form these assemblies in solution without organic ligands. Thatis, arrays of nanoparticles from crystallization methods are usuallysurrounded by organic ligands that interfere with further chemicalprocessing and can limit durability. Organic ligands typically melt fromheat and darken in the presence of light or absorb at wavelengths ofinterest. This lack of thermal and optical stability makes avoidingorganic ligands crucial for environmentally robust structures.

Also, existing approaches for forming packed nanoparticles do not formassemblies with a high degree of perfection (smoothness and sphericity)and size selectivity.

Agglomerated nanoparticles may be formed without organic ligands byadjusting the pH of a solution of dispersed nanoparticles with an acidor base solution to near the isoelectric point of the nanoparticles.However, these nanoparticles will not be tightly packed.

Nanoparticles may be formed in an array requiring a substrate. In theseapproaches, nanoparticles are packed via drying from a solution(colloidal crystals) or electrophoresis, both requiring a substrate.Colloidal crystals are formed by dispersing colloids in a solution anddrying on a substrate or spin coating on a substrate. Moreover,electrophoresis does not always result in tightly packed nanoparticles.

Arrays of nanoparticles may be grown in an array on a substrate from aprocess with gaseous reactants. Arrays of nanoparticles may be formedthrough a wet chemical process. In one approach, metals or oxides aredeposited in the pores of anodic alumina or mesoporous silica. Thisapproach forms either single layers of nanorods or nanorods that haveempty space between them and no material between the rods. This resultsin a low density of material and reduced efficacy from the array.

The packed arrays of nanoparticles, as taught in the prior art, tend tobe non-uniform in array size and shape. In order to be useful in largerdevices, arrays of assembled particles should be uniform in size andshape. This is necessary for either bottom-up assembly processes, suchas self-assembly into larger assemblies; for top-down assemblyprocesses, such as pick-and-place assembly onto patterned substrates; orfor combinations of bottom-up and top-down assembly.

There is a desire for monodisperse, tightly packed, smooth, and organicligand-free assemblies of nanoparticles. These assemblies would beuseful for optical, magnetic, and electronic device applications, amongothers. Methods to make these assemblies are sought.

SUMMARY OF THE INVENTION

The present invention addresses the aforementioned needs in the art, aswill now be summarized and then further described in detail below.

Some variations of the invention provide an interspersed assembly ofnanoparticles, the interspersed assembly comprising a first phasecontaining first nanoparticles with an average first-nanoparticlediameter and a second phase containing second nanoparticles with anaverage second-nanoparticle diameter, wherein the second phase isinterspersed with the first phase, wherein the first nanoparticles arecompositionally different than the second nanoparticles, wherein theinterspersed assembly has a volume from 1 μm³ to 1 mm³, wherein theinterspersed assembly has a packing fraction from 20% to 100%, andwherein the interspersed assembly has an average relative surfaceroughness less than 5%.

In some embodiments, the ratio of the average first-nanoparticlediameter to the average second-nanoparticles diameter is selected fromabout 1.1 to about 100.

In some embodiments, the ratio of the volume of the first phase to thevolume of the second phase is selected from about 0.1 to about 10, suchas about 0.5 to about 8.

In some embodiments, the interspersed assembly is a semi-orderedassembly comprising discrete particles of the first phase, wherein thediscrete particles are surrounded by a continuous phase of the secondphase. In certain embodiments of a semi-ordered assembly, the averageseparation between the discrete particles is about 20% to about 1000% ofthe average first-nanoparticle diameter.

The first nanoparticles and the second nanoparticles may each contain amaterial independently selected from the group consisting of metals,metal oxides, metal fluorides, metal sulfides, metal phosphides,ceramics, glasses, polymers, and combinations thereof.

In certain embodiments, the first nanoparticles contain SiO₂, and thesecond nanoparticles contain TiO₂, ZnO, LiYF₄, or a combination thereof.

In some embodiments, the first nanoparticles are non-spherical. In theseor other embodiments, the second nanoparticles are non-spherical. Incertain embodiments, both of the first nanoparticles and the secondnanoparticles are non-spherical. In different embodiments, both of thefirst nanoparticles and the second nanoparticles are spherical orapproximately spherical.

The overall interspersed assembly is spherical or approximatelyspherical, in preferred embodiments of the invention. Non-sphericalinterspersed assemblies are also provided.

In some embodiments, the packing fraction is at least 90%, at least 95%,or at least 99%.

In some embodiments, the average relative surface roughness is less than2%, less than 1%, less than 0.5%, or less than 0.1%. “Relative surfaceroughness” is defined as a ratio of the size of a protrusion on thesurface to the diameter of the assembly.

The interspersed assembly is free of organic ligands, in certainembodiments.

The interspersed assembly is not disposed on a substrate, in certainembodiments.

Other variations of the invention provide a core-shell assembly ofnanoparticles, the core-shell assembly comprising a first phasecontaining first nanoparticles with an average first-nanoparticlediameter and a second phase containing second nanoparticles with anaverage second-nanoparticle diameter, wherein the second phase forms ashell surrounding a core of the first phase, wherein the firstnanoparticles are compositionally different than the secondnanoparticles, wherein the core-shell assembly has a volume from 1 μm³to 1 mm³, wherein the core-shell assembly has a packing fraction from20% to 100%, and wherein the core-shell assembly has an average relativesurface roughness less than 5%.

In some embodiments, the ratio of the average first-nanoparticlediameter to the average second-nanoparticles diameter is selected fromabout 1.1 to about 100.

In some embodiments of core-shell assemblies, the ratio of the volume ofthe first phase to the volume of the second phase is selected from about0.1 to about 1.0.

In the core-shell assembly, the core may contain a mass ratio of thefirst nanoparticles to the second nanoparticles of at least 5, while theshell may contain a mass ratio of the second nanoparticles to the firstnanoparticles of at least 5.

In some embodiments of core-shell assemblies, the first nanoparticlesand the second nanoparticles each contain a material independentlyselected from the group consisting of metals, metal oxides, metalfluorides, metal sulfides, metal phosphides, ceramics, glasses,polymers, and combinations thereof.

In certain core-shell assemblies, the first nanoparticles contain SiO₂,and the second nanoparticles contain TiO₂, ZnO, LiYF₄, or a combinationthereof

In some core-shell assemblies, the first nanoparticles arenon-spherical. In these or other embodiments, the second nanoparticlesare non-spherical. In certain embodiments, both of the firstnanoparticles and the second nanoparticles are non-spherical. Indifferent embodiments, both of the first nanoparticles and the secondnanoparticles are spherical or approximately spherical.

The overall core-shell assembly is spherical or approximately spherical,in preferred embodiments of the invention. Non-spherical core-shellassemblies are also provided.

In some embodiments of core-shell assemblies, the packing fraction is atleast 90%, at least 95%, or at least 99%.

In some embodiments of core-shell assemblies, the average relativesurface roughness is less than 2%, less than 1%, less than 0.5%, or lessthan 0.1%.

The core-shell assembly is free of organic ligands, in certainembodiments.

The core-shell assembly is not disposed on a substrate, in certainembodiments.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is an exemplary method flowchart for assembling particles, insome embodiments of the invention.

FIG. 2 is a schematic diagram of a method (and a system) for assemblinga plurality of particles into elongated assemblies throughone-dimensional confined droplet dissolution, in some embodiments.

FIG. 3 is a schematic diagram of a method (and a system) for assemblinga plurality of particles into biconvex lens-shaped assemblies throughtwo-dimensional confined droplet dissolution, in some embodiments.

FIG. 4 is a schematic diagram of a continuous-flow microfluidic system(and a method) for assembling a plurality of particles into particleassemblies, in some embodiments.

FIG. 5 is a SEM image (scale bar=10 μm) of an illustrative PbS particleassembly fabricated in Example 1.

FIG. 6 is a SEM image (scale bar=2 microns) of a semi-orderedinterspersed assembly containing SiO₂ surrounded by LiYF₄, in Example 2.

FIG. 7 is a SEM image (scale bar=2 microns) of a semi-orderedinterspersed assembly containing SiO₂ surrounded by TiO₂, in Example 3.

FIG. 8 is a SEM image (scale bar=4 microns) of an interspersed assemblycontaining SiO₂ surrounded by ZnO, in Example 4.

FIG. 9 is a SEM image (scale bar=5 microns) of an interspersed assemblycontaining SiO₂ surrounded by TiO₂, in Example 5.

FIG. 10 is a SEM image (scale bar=5 microns) of a core-shell assemblycontaining a core of primarily SiO₂ (right-hand side of image)surrounded by a shell of primarily TiO₂ (left-hand side of image), inExample 6.

FIG. 11 is a SEM image (scale bar=5 microns) of a core-shell assemblycontaining a core of primarily SiO₂ (top of image) surrounded by a shellof primarily TiO₂ (bottom of image), in Example 7.

FIG. 12 is a SEM image (scale bar=10 microns) of a core-shell assemblycontaining a core of primarily SiO₂ surrounded by a shell of primarilyLiYF₄, in Example 8 of the invention.

FIG. 13 is a SEM image (scale bar=50 microns) of a plurality ofspherical or approximately spherical assemblies that each have discreteSiO₂ nanoparticles and a semi-continuous phase of LiYF₄ nanoparticles,in Example 9.

FIG. 14 is a SEM image (scale bar=1 micron) of an individual assembly(one of the spheres of FIG. 13 ) showing discrete SiO₂ nanoparticles anda semi-continuous phase of LiYF₄ nanoparticles, in Example 9.

FIG. 15 is a SEM image (scale bar=10 microns) of approximately sphericalcore-shell assemblies with LiYF₄ (core) and TiO₂ (shell), in Example 10.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The structures, systems, compositions, and methods of the presentinvention will be described in detail by reference to variousnon-limiting embodiments.

This description will enable one skilled in the art to make and use theinvention, and it describes several embodiments, adaptations,variations, alternatives, and uses of the invention. These and otherembodiments, features, and advantages of the present invention willbecome more apparent to those skilled in the art when taken withreference to the following detailed description of the invention inconjunction with the accompanying drawings.

As used in this specification and the appended claims, the singularforms “a,” “an,” and “the” include plural referents unless the contextclearly indicates otherwise. Unless defined otherwise, all technical andscientific terms used herein have the same meaning as is commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs.

Unless otherwise indicated, all numbers expressing conditions,concentrations, dimensions, and so forth used in the specification andclaims are to be understood as being modified in all instances by theterm “about.” Accordingly, unless indicated to the contrary, thenumerical parameters set forth in the following specification andattached claims are approximations that may vary depending at least upona specific analytical technique.

The term “comprising,” which is synonymous with “including,”“containing,” or “characterized by” is inclusive or open-ended and doesnot exclude additional, unrecited elements or method steps. “Comprising”is a term of art used in claim language which means that the named claimelements are essential, but other claim elements may be added and stillform a construct within the scope of the claim.

As used herein, the phrase “consisting of” excludes any element, step,or ingredient not specified in the claim. When the phrase “consists of”(or variations thereof) appears in a clause of the body of a claim,rather than immediately following the preamble, it limits only theelement set forth in that clause; other elements are not excluded fromthe claim as a whole. As used herein, the phrase “consisting essentiallyof” limits the scope of a claim to the specified elements or methodsteps, plus those that do not materially affect the basis and novelcharacteristic(s) of the claimed subject matter.

With respect to the terms “comprising,” “consisting of,” and “consistingessentially of,” where one of these three terms is used herein, thepresently disclosed and claimed subject matter may include the use ofeither of the other two terms, except when used in Markush groups. Thusin some embodiments not otherwise explicitly recited, any instance of“comprising” may be replaced by “consisting of” or, alternatively, by“consisting essentially of.”

Some variations provide methods for assembling particles into tightlypacked structures with controlled order and complexity. An emulsion ofparticle-containing droplets is created, followed by dissolution of theliquid into the continuous phase , causing particle assembly. Thisdisclosure provides methods to form various particle assemblies, andparticle assemblies obtained therefrom. Assemblies may be formed frommultiple types or compositions of nanoparticles, forming core-shellstructures or interspersed structures, such as semi-ordered interspersedstructures.

Distinct solvents may be utilized for the assembly process, wherein asolvent for droplet formation is different than a co-solvent for dropletdissolution. This increases control of the dissolving-droplet processand enables a much broader set of materials to be assembled. Theco-solvent helps keep nanoparticles suspended in a droplet when water isnot an ideal solvent.

In some variations of this invention, a single solvent is utilized. Forexample, water as the sole solvent may be utilized. When water alone isnot a sufficient solvent for any reason, a co-solvent such as dimethylsulfoxide may be utilized.

Some variations of the invention provide an interspersed assembly ofnanoparticles, the interspersed assembly comprising a first phasecontaining first nanoparticles with an average first-nanoparticlediameter and a second phase containing second nanoparticles with anaverage second-nanoparticle diameter, wherein the second phase isinterspersed with the first phase, wherein the first nanoparticles arecompositionally different than the second nanoparticles, wherein theinterspersed assembly has a volume from 1 μm³ to 1 mm³, wherein theinterspersed assembly has a packing fraction from 20% to 100%, andwherein the interspersed assembly has an average relative surfaceroughness less than 5%.

The first-nanoparticle diameter may be selected from about 10 nanometersto about 5000 nanometers, for example. In various embodiments, thefirst-nanoparticle diameter is about, at least about, or at most about10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 300,400, 500, 600, 700, 800, 900, 1000, or 2000 nanometers, including allintervening ranges.

The second-nanoparticle diameter may be selected from about 2 nanometersto about 1000 nanometers, for example. In various embodiments, thesecond-nanoparticle diameter is about, at least about, or at most about2, 5, 10, 20, 30, 40, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 300,400, 500, 600, 700, 800, 900, or 1000, including all intervening ranges.

In some embodiments, the ratio of the average first-nanoparticlediameter to the average second-nanoparticles diameter is selected fromabout 1.1 to about 1000. In various embodiments, the ratio of theaverage first-nanoparticle diameter to the average second-nanoparticlesdiameter is about, at least about, or at most about 1.1, 1.5, 2, 3, 4,5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400,or 500, including all intervening ranges.

In some embodiments, the ratio of the volume of the first phase to thevolume of the second phase is selected from about 0.1 to about 10, suchas about 0.5 to about 8. In various embodiments, the ratio of the volumeof the first phase to the volume of the second phase is about, at leastabout, or at most about 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.9, 1.0, 1.1,1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10, including allintervening ranges. In other embodiments, the ratio is greater than 10,such as about 25, 50, or 100.

In some embodiments, the interspersed assembly is a semi-orderedassembly comprising discrete particles of the first phase, wherein thediscrete particles are surrounded by a continuous or semi-continuousamount of the second phase. In some embodiments, “semi-ordered” meansthere is a narrow standard deviation of separation between discreteparticles, such as (but not limited to) 0.5±0.2 particle widths ofseparation between the edges of particles. In certain embodiments of asemi-ordered assembly, the average separation between the discreteparticles is about 20% to about 1000% of the average first-nanoparticlediameter. In various embodiments of a semi-ordered assembly, the averageseparation between the discrete particles is about, at least about, orat most about 25%, 50%, 75%, 100%, 150%, 200%, 250%, 300%, 400%, 500%,600%, 700%, 800%, or 900% (including all intervening ranges) of theaverage first-nanoparticle diameter.

The first nanoparticles and the second nanoparticles may each contain amaterial independently selected from the group consisting of metals,metal oxides, metal fluorides, metal sulfides, metal phosphides,ceramics, glasses, polymers, and combinations thereof.

In certain embodiments, the first nanoparticles contain SiO₂, and thesecond nanoparticles contain TiO₂, ZnO, LiYF₄, or a combination thereof.

In some embodiments, the first nanoparticles are non-spherical. In theseor other embodiments, the second nanoparticles are non-spherical. Incertain embodiments, both of the first nanoparticles and the secondnanoparticles are non-spherical. In different embodiments, both of thefirst nanoparticles and the second nanoparticles are spherical orapproximately spherical.

The overall interspersed assembly is spherical or approximatelyspherical, in preferred embodiments of the invention. Non-sphericalinterspersed assemblies are also provided. For example, an interspersedassembly may be in the shape of a torus (an ideal torus has a sphericityof 0.89 and is thus not approximately spherical in this disclosure).

In some embodiments, the packing fraction is at least 90%, at least 95%,or at least 99%. In some embodiments, the average relative surfaceroughness is less than 2%, less than 1%, less than 0.5%, or less than0.1%. The interspersed assembly is free of organic ligands, in certainembodiments. The interspersed assembly is not disposed on a substrate,in certain embodiments.

Other variations of the invention provide a core-shell assembly ofnanoparticles, the core-shell assembly comprising a first phasecontaining first nanoparticles with an average first-nanoparticlediameter and a second phase containing second nanoparticles with anaverage second-nanoparticle diameter, wherein the second phase forms ashell surrounding a core of the first phase, wherein the firstnanoparticles are compositionally different than the secondnanoparticles, wherein the core-shell assembly has a volume from 1 μm³to 1 mm³, wherein the core-shell assembly has a packing fraction from20% to 100%, and wherein the core-shell assembly has an average relativesurface roughness less than 5%.

In some embodiments of core-shell assemblies, the ratio of the averagefirst-nanoparticle diameter to the average second-nanoparticles diameteris selected from about 1.1 to about 100. In various embodiments, theratio of the average first-nanoparticle diameter to the averagesecond-nanoparticles diameter is about, at least about, or at most about1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90,100, 200, 300, 400, or 500, including all intervening ranges.

In some embodiments of core-shell assemblies, the ratio of the volume ofthe first phase to the volume of the second phase is selected from about0.1 to about 10. In various embodiments, the ratio of the volume of thefirst phase to the volume of the second phase is about, at least about,or at most about 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2,1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10, including all interveningranges. In other embodiments, the ratio is greater than 10, such asabout 25, 50, or 100.

It has been discovered that the ratio of first/second nanoparticle sizesand the ratio of first/second phase volumes are both important becausethese parameters influence whether the assembly is a core-shellassembly, an interspersed assembly, or a hybrid of the two types ofassemblies. For example, and without limitation, if the ratio of theaverage first-nanoparticle diameter to the average second-nanoparticlesdiameter is at least 2, then (a) an interspersed structure is expectedto form if the ratio of volume of the first phase to the volume of thesecond phase is about 0.7 or greater (increasing amounts of the largerfirst nanoparticles); and (b) a core-shell structure is expected to formif the ratio of volume of the first phase to the volume of the secondphase is less than about 0.7 (increasing amounts of the smaller secondnanoparticles). These assembly heuristics are disclosed as a guide forthe skilled artisan to design particle assemblies and are based onexperimental results (see Examples herein) but are not intended to limitthe invention in any way.

In a core-shell assembly, the core may contain a mass ratio of the firstnanoparticles to the second nanoparticles of at least 5 or at least 10,while the shell may contain a mass ratio of the second nanoparticles tothe first nanoparticles of at least 5 or at least 10. If the corecontains first nanoparticles but no second nanoparticles, and the shellcontains second nanoparticles but no first nanoparticles, these ratiosare infinite.

In some embodiments of core-shell assemblies, the first nanoparticlesand the second nanoparticles each contain a material independentlyselected from the group consisting of metals, metal oxides, metalfluorides, metal sulfides, metal phosphides, ceramics, glasses,polymers, and combinations thereof.

In certain core-shell assemblies, the first nanoparticles contain SiO₂,and the second nanoparticles contain TiO₂, ZnO, LiYF₄, or a combinationthereof

In some core-shell assemblies, the first nanoparticles arenon-spherical. In these or other embodiments, the second nanoparticlesare non-spherical. In certain embodiments, both of the firstnanoparticles and the second nanoparticles are non-spherical. Indifferent embodiments, both of the first nanoparticles and the secondnanoparticles are spherical or approximately spherical.

The overall core-shell assembly is spherical or approximately spherical,in preferred embodiments of the invention. Non-spherical core-shellassemblies are also provided. For example, a core-shell assembly may bein the shape of a torus.

In some embodiments of core-shell assemblies, the packing fraction is atleast 90%, at least 95%, or at least 99%. In some embodiments ofcore-shell assemblies, the average relative surface roughness is lessthan 2%, less than 1%, less than 0.5%, or less than 0.1%. The core-shellassembly is free of organic ligands, in certain embodiments. Thecore-shell assembly is not disposed on a substrate, in certainembodiments.

The smoothness achievable with the methods of the invention makes thesematerials useful as optical components, such as wavelength-specificscatterers, lenses, prisms, and retroreflectors. For example, assemblingoptical components from nanoparticles enables (i) the use of materialssuch as laser glasses LiYF₄ and NaYF₄ that are difficult to grow inlarge volumes and (ii) the fabrication of discrete optics at a lengthscale smaller than is possible with traditional machining and polishing.The principles of the invention enable a bottom-up process to producemicro-sized infrared lens materials (e.g., lenses less than 10 micronsin thickness).

In preferred embodiments that do not employ organic ligands,infrared-transparent lens materials or other infrared optics may befabricated, with the benefit that there are no infrared absorptions fromorganic ligands. IR-scattering structures with selected wavelengths ofscattering are important for temperature control of orbital platforms,for example.

The disclosed methods are amenable to the addition of complex featuresto the assemblies, such as nanoparticle shells or assembly in confinedspaces to form complex morphologies.

Some variations provide tightly-packed, smooth, and organic ligand-freeassemblies of nanoparticles. In some embodiments, the assemblies arehighly spherical, even when the nanoparticles are asymmetric. In someembodiments, the assemblies are non-spherical. In some embodiments,core-shell assemblies are provided.

In some embodiments, assemblies of nanoparticles are utilized forpharmaceutical manufacture.

Some variations provide a method of assembling a plurality of particlesinto particle assemblies, the method comprising:

-   -   (a) obtaining a first fluid containing particles and a solvent        for the particles;    -   (b) obtaining a second fluid, wherein the first fluid is not        fully miscible in the second fluid;    -   (c) obtaining a third fluid that is a co-solvent for the first        fluid and the second fluid;    -   (d) combining the first fluid and the second fluid to generate        an emulsion containing a dispersed phase of droplets of the        first fluid in the second fluid;    -   (e) adding the third fluid to the emulsion; and    -   (f) dissolving the solvent from the droplets into a mixture of        the second fluid and the third fluid, thereby forming particle        assemblies.

The first fluid contains the particles to be assembled. The particlesmay be of a single composition or multiple compositions, such as thosedisclosed below. Also, the particles may be of a single shape ormultiple shapes, such as those disclosed below.

The concentration of particles in the first fluid may be from about 1mg/mL to about 100 mg/mL, such as about 5, 10, 20, 30, 40, 50, 60, 70,80, or 90 mg/mL. Concentrations lower than 1 mg/mL or higher than 100mg/mL are possible, depending on the rate of assembly, the type ofparticles, and the desired final assemblies.

In some embodiments, the average size of the particles is from about 1nanometer to about 100 microns. The “average size” is the averagediameter for spherical particles or the average effective diameter fornon-spherical particles (effective diameter is the cube root of 6 V/π,where V is the particle volume). In certain embodiments, the particlesare nanoparticles with an average size from about 1 nanometer to about1000 nanometers, such as from about 5 nm to about 1000 nm, about 10 nmto about 1000 nm, about 50 nm to about 1000 nm, or about 100 nm to about1000 nm. In certain preferred embodiments, all of the particles arenanoparticles. The particle size is the particle diameter for sphericalparticles, or length or effective diameter for other particlegeometries. In some embodiments, all of the particles have substantiallysimilar size.

Particles sizes may be measured by a variety of techniques, includingdynamic light scattering, laser diffraction, image analysis, or sieveseparation, for example. Dynamic light scattering is a non-invasive,well-established technique for measuring the size and size distributionof particles typically in the submicron region, and with the latesttechnology down to 1 nanometer. Laser diffraction is a widely usedparticle-sizing technique for materials ranging from hundreds ofnanometers up to several millimeters in size. Exemplary dynamic lightscattering instruments and laser diffraction instruments for measuringparticle sizes are available from Malvern Instruments Ltd.,Worcestershire, UK. Image analysis to estimate particle sizes anddistributions can be done directly on photomicrographs, scanningelectron micrographs, or other images. Finally, sieving is aconventional technique of separating particles by size.

Generally, particles may be round, cylindrical, elliptical,diamond-shaped, tetragonal, tetragonal bipyramidal, cubic, or hexagonalprism structures wherein the ratio between the shortest and longestdimension is 1:1 to 1:5. The particles may be symmetric or asymmetric. Amixture of solvents in the discrete phase is preferred for assembly ofasymmetric particles.

The particles may be selected from the group consisting of metals,ceramics, glasses, and polymers; oxides, fluorides, sulfides, orphosphides thereof; and combinations of the foregoing. For example, theparticles may include oxides, fluorides, sulfides, or phosphides of ametal or metalloid. In the case of particles containing polymers, thepolymers may be insulators, semiconductors, or conductors (i.e.,intrinsically conducting polymers). In various embodiments, hydrophobicparticles are utilized. In some embodiments, moderately hydrophilicparticles are utilized. In certain embodiments, oxidation-sensitiveparticles (e.g., PbS or PbSe particles) are used to make particleassemblies.

The particles may contain charged surface groups to enable the particlesto be dispersed in a solvent. For example, charged surface groups may beselected from thiocyanate (SCN⁻), borofluoride (e.g., tetrafluoroborate,BF₄ ⁻), or hexafluorophosphate (PF₆ ⁻). In some embodiments, theparticles initially are covered in organic ligands such as oleic acidand undergo a ligand-exchange process to replace the ligands withmore-polar ligands, which may be inorganic polar ligands. The startingligands may also be inorganic ligands. The particles may beligand-exchanged to render the particles soluble in the first fluid,before or during step (a). For example, the particles may beligand-exchanged to replace a starting ligand (e.g., a starting organicligand) with an inorganic ligand selected from the group consisting ofthiocyanate, borofluoride, hexafluorophosphate, and combinationsthereof.

In preferred embodiments, fully formed particles are provided forpurposes of assembly, rather than combining the synthesis of theparticles with the assembly process.

In some embodiments, the particles include more than one type ofmaterial. For example, the particles may have a core-shell configurationwith one material in the core and a different material in the shell. Incertain embodiments, the starting particles are Janus particles with twodistinct materials present in each particle, such that each particlesurface has two or more distinct physical properties.

The solvent for the particles, in the first fluid, may be selected fromthe group consisting of water, formamide, alkyl formamide (e.g., methylformamide), dialkyl formamide (e.g., dimethyl formamide), dialkylsulfoxide (e.g., dimethyl sulfoxide), acetonitrile, methanol, ethanol,isopropanol, 1-propanol, isobutanol, 1-butanol, 2-butanol, t-butanol,acetone, tetrahydrofuran, and combinations thereof. In some embodiments,the solvent is an aqueous solvent that contains water and at least oneother species that is miscible in water. In some embodiments, thesolvent is an anhydrous solvent that contains less than 1 vol %, lessthan 0.1 vol %, less than 0.05 vol %, or less than 0.01 vol % water.

During step (a), and/or prior to step (d), electrostatic repulsion,Brownian motion, sonication, bulk mixing (e.g., agitation or vesselrotation), and/or gas sparging, for example, may be used to keep theparticles suspended in the solution of the first fluid.

The method may further include adjusting pH of the first fluid, prior tostep (d). The pH of first fluid may be adjusted for particlesuspendibility, to inhibit electrostatic assembly, or to inducemulti-particle co-assembly, for example.

The particles may be dispersed in the first fluid by adjusting the pH toincrease the zeta potential. Preferably, the particles in the firstfluid exhibit a zeta potential of at least ±15 mV. In this disclosure,the notation “±15 mV” (for example) in reference to zeta potential meansthat the zeta potential is 15 mV in magnitude (absolute value) and maybe either +15 mV or −15 mV; this does not refer to a range of valuesbetween −15 mV to 15 mV. A zeta potential of at least ±15 mV means thezeta potential is either +15 mV, or greater, or −15 mV, or morenegative.

A pH-adjustment substance may be included in the first fluid. ApH-adjustment substance is a chemical that adjusts the pH of a solution,either down (more acidic) or up (more alkaline). The pH-adjustmentsubstance may be an acid or a base. The zeta potential of the particlesmay be adjusted with pH. In some embodiments, the pH is adjusted to avalue that is at least ±3 pH units away from the isoelectric point ofthe particles to be suspended or dissolved. In these or otherembodiments, the zeta potential of the particles may be adjusted with amiscible solvent, or mixture of miscible solvents, to encourage betterdissolution or suspendibility.

The second fluid may be an alcohol, a ketone, an ester (e.g., analiphatic ester), an alkane (e.g., a cyclic alkane), or an acetate(e.g., an alkyl acetate), for example. In some embodiments, the secondfluid is selected from the group consisting of methyl laurate,1-butanol, t-butanol, 1-octanol, 1-hexanol, 1-decanol, ethyl ether,dibutyl ether, dihexyl ether, dioctyl ether, methyl t-butyl ether,methyl ethyl ketone, methyl amyl ketone, cyclohexane, ethyl acetate, andcombinations thereof.

The first fluid and second fluid are not fully miscible with each other.In some embodiments, the first fluid is completely insoluble in thesecond fluid. In other embodiments, the first fluid is slightly solublein the second fluid. The first fluid is preferably from about 0 vol % toabout 20 vol % soluble in the second fluid, more preferably from about0.1 vol % to about 15 vol % soluble in the second fluid, and mostpreferably from about 1 vol % to about 10 vol % soluble in the secondfluid. These percentages are on a volume/volume basis, i.e. calculatedas the volume of the first fluid that dissolves in a given volume of thesecond fluid.

The third fluid may be an alcohol, a ketone, an ester (e.g., analiphatic ester), an alkane (e.g., a cyclic alkane), or an acetate(e.g., an alkyl acetate), for example. In some embodiments, the thirdfluid is selected from the group consisting of 1-octanol, 1-butanol,t-butanol, 1-hexanol, 1-decanol, ethyl ether, dibutyl ether, dihexylether, dioctyl ether, methyl t-butyl ether, methyl ethyl ketone,cyclohexane, ethyl acetate, and combinations thereof.

The third fluid may be an alcohol, an ester (e.g., an aliphatic ester,such as but not limited to methyl laurate), a ketone, an alkane, or acyclic alkane, for example. In some embodiments, the third fluid isselected from the group consisting of methyl laurate, 1-butanol,t-butanol, 1-octanol, 1-hexanol, 1-decanol, ethyl ether, dibutyl ether,dihexyl ether, dioctyl ether, methyl t-butyl ether, methyl ethyl ketone,methyl amyl ketone, cyclohexane, ethyl acetate, and combinationsthereof.

Preferably, the first fluid is at least partially soluble in the thirdfluid, and more preferably the first fluid is completely miscible withthe third fluid. In some embodiments, the first fluid has a solubilityin the third fluid from about 1 vol % to about 100 vol % (completelymiscible), such as about 5 vol %, 10 vol %, 20 vol %, 30 vol %, 40 vol%, 50 vol %, 60 vol %, 70 vol %, 80 vol %, or 90 vol %. Thesepercentages are on a volume/volume basis, i.e. calculated as the volumeof the second fluid that dissolves in a given volume of the third fluid.

Preferably, the second fluid is at least partially soluble in the thirdfluid, and more preferably the second fluid is completely miscible withthe third fluid. In some embodiments, the second fluid has a solubilityin the third fluid from about 10 vol % to about 100 vol % (completelymiscible), such as about 20 vol %, 30 vol %, 40 vol %, 50 vol %, 60 vol%, 70 vol %, 80 vol %, or 90 vol %. These percentages are on avolume/volume basis, i.e. calculated as the volume of the second fluidthat dissolves in a given volume of the third fluid.

The third fluid is a co-solvent for the first and second fluids. Thatis, the first and second fluids are each at least partially soluble inthe third fluid, as noted above. In some embodiments, the third fluid isa fully miscible co-solvent for both the first and second fluids.Because the third fluid is a co-solvent, the first fluid is at leastslightly soluble (or even fully miscible) in a mixture of the secondfluid and the third fluid—despite that the first and second fluids arenot fully miscible and may even be completely insoluble with each other.

In some embodiments, the third fluid is selected to improve thesolubility of the particles in the first fluid.

An interface-stabilization substance (e.g., a surfactant) may becontained within the first fluid and/or the second fluid. It ispreferable to include the interface-stabilization substance, whenpresent, in the second fluid. The interface-stabilization substancesegregates to interfaces between the first fluid and the second fluid.The interface-stabilization substance may be selected from cationic,anionic, zwitterionic, or nonionic surfactants. In preferredembodiments, the interface-stabilization substance is a nonionicsurfactant (e.g., polyglycerol alkyl ethers, polyoxyethylene alkylethers, or polysorbates). In some embodiments, theinterface-stabilization substance is selected from particles, such asfunctionalized particles (e.g., Fe₃O₄ particles functionalized withpolyacrylic acid).

In some embodiments, step (d) includes a step selected from the groupconsisting of vortex mixing, ultrasonic mixing, impeller mixing,microfluidizing, microfluidics droplet generation, porous-glass dropletgeneration, and combinations thereof. The speed of mixing and/or amountof shear energy may be used to control the droplet volume, andthus—along with particle concentration—control the assembly volume.

In step (f), the droplets may be agitated, such as by electrostaticrepulsion, Brownian motion, stirring, shaking, rolling, rotating, and/orsonication. When agitation is employed, the degree of agitation shouldbe high enough to promote convection and dissolution (and avoidagglomeration), but not so high to shear the droplets into finerdroplets, which would increase the assembly dispersity index in thefinal assemblies. Preferably, the droplets do not coalesce during thetime period for dissolution.

Step (f) may be conducted for a dissolving time (time period fordissolution) from about 1 second to about 10 hours, for example. Invarious embodiments, the method employs a dissolving time of about 10seconds, 30 seconds, 1 minute, 2 minutes, 5 minutes, 10 minutes, 30minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, or 8 hours.

Step (f) may be conducted at a dissolving temperature from about −15° C.to about 150° C. In various embodiments, the method employs a dissolvingtemperature of about −10° C., −5° C., 0° C., 5° C., 10° C., 15° C., 20°C., 25° C., 30° C., 40° C., 50° C., 60° C., 70° C., 80° C., 90° C., 100°C., 110° C., 120° C., 130° C., or 140° C. The dissolving temperature maybe as low as a temperature just above the freezing point of the fluidmixture. Optionally, a temperature profile is utilized during step (f),with increasing or decreasing temperature to adjust solubilityproperties. The dissolving temperature may be lower or higher than othertemperatures utilized during the method.

In some embodiments, steps (d), (e), and (f) are continuous. In otherembodiments, steps (d), (e), and (f) are conducted in batch.Combinations are possible, including semi-continuous, semi-batch, or amethod in which one or more steps are done in batch while one or moresteps are performed continuously. As one example, steps (d) and (e)could be a batch process to make the emulsion and combine it with thethird fluid, creating an intermediate mixture. The intermediate mixturecould then be continuously fed to a droplet-dissolving region tocontinuously form particle assemblies.

The assembly of the particles, in various embodiments, is characterizedby an assembly rate (particles assembled per second) of about 10⁶, 10⁷,10⁸, 10⁹, 10¹⁰, 10¹¹, 10¹² particles/second or higher.

The particle assemblies are optionally separated from the solution, suchas by centrifugation or filtration, for example. The particle assembliesare optionally dried to remove any residual fluid. Drying may beperformed with heat and/or a vacuum. In some embodiments, the particleassemblies are freeze-dried.

In some embodiments, in step (f), the number of particle assembliesequals the number of droplets. In some embodiments, the number of theparticle assemblies is less than the number of the droplets. If theinitial droplets all contain the same particle mass, then the finalparticle assemblies are expected to be nearly monodisperse, i.e. anassembly dispersity index close to or at 0. As used herein, the“assembly dispersity index” is the ratio of standard deviation ofassembly volume to the mean of the assembly volume, calculated over allassemblies present. In some embodiments, the assembly dispersity indexof the particle assemblies is less than 0.2, preferably less than 0.1,and more preferably less than 0.05.

See FIG. 1 , which is an exemplary method flowchart for assemblingparticles, in some variations.

FIG. 2 is a schematic diagram of a method 200 (and a system) forassembling a plurality of particles into elongated assemblies throughone-dimensional confined droplet dissolution, in some embodiments. InFIG. 2 , a droplet 204 contains a first fluid of particles 201 dissolvedor suspended in a solvent 202. The droplet 204 is surrounded by a secondfluid 203. An emulsion is formed with many droplets 204 in a continuousphase of the second fluid 203. An optional first flat plate 205 and anoptional second flat plate 206 confine the droplet 204 (the flat plates205 and 206 are not necessary). A third fluid is added to the emulsion(or equivalently, the emulsion is added to the third fluid). The thirdfluid is a co-solvent for the first and second fluids. The result is acombination 209 of the second and third fluids. After a period of time207, and/or following conveying 207 the droplet 204 to anothercontainer, the droplet 210 begins to elongate, due to the spatiallynon-uniform dissolution rates caused by the flat plates 205 and 206. Thesolvent 202 contained initially in droplet 204 is transported out of thedissolving droplet 210, as depicted by the outward arrows in FIG. 2 ,into third fluid 209. A liquid phase 208 remains in the dissolvingdroplet 210 until the assembly 212 is formed. After a period of time211, and/or following conveying 211 the dissolving droplet 210 toanother container, an elongated assembly 212 is formed, contained in aliquid mixture 213 that is or contains a mixture of solvent 202, secondfluid 203, and third fluid 209. The elongated assembly 212 may berecovered from liquid mixture 213 such as by filtering, centrifuging,drying, or other recovery steps.

FIG. 3 is a schematic diagram of a method 300 (and a system) forassembling a plurality of particles into biconvex lens-shaped assembliesthrough two-dimensional confined droplet dissolution, in someembodiments. In FIG. 3 , a droplet 304 contains a first fluid ofparticles 301 dissolved or suspended in a solvent 302. The droplet 304is surrounded by a second fluid 303. An emulsion is formed with manydroplets 304 in a continuous phase of the second fluid 303. An optionaltubular geometry 305 confines the droplet 304. A third fluid is added tothe emulsion (or equivalently, the emulsion is added to the thirdfluid). The third fluid is a co-solvent for the first and second fluids.The result is a combination 308 of the second and third fluids. After aperiod of time 306, and/or following conveying 306 the droplet 304 toanother container, the droplet 309 begins to elongate and form convexregions (that is, interior angles less than 180°) on opposite sides, dueto the dimensional constraints imposed by tubular geometry 305. Thesolvent 302 contained initially in droplet 304 is transported out of thedissolving droplet 309, as depicted by the outward arrows in FIG. 3 ,into third fluid 308. A liquid phase 307 remains in the dissolvingdroplet 309 until the assembly 311 is formed. After a period of time310, and/or following conveying 310 the dissolving droplet 309 toanother container, a biconvex lens-shaped assembly 311 is formed,contained in a liquid mixture 312 that is or contains a mixture ofsolvent 302, second fluid 303, and third fluid 308. The biconvexlens-shaped assembly 311 may be recovered from liquid mixture 312 suchas by filtering, centrifuging, drying, or other recovery steps.

In some embodiments of the invention, droplet microfluidics are utilizedto generate the emulsion containing a dispersed phase of droplets of thefirst fluid in the second fluid. For example, the first and secondfluids may be introduced (such as by liquid flow or by dropping thedroplets through air) into a microfluidic droplet-generating region,thereby generating a dispersed phase of the first fluid within thesecond fluid (i.e., an emulsion). This emulsion is conveyed from thedroplet-generating region to a droplet-dissolving region to be combinedwith the third fluid. The third fluid may be added to thedroplet-dissolving region prior to introduction of the emulsion.Alternatively, or additionally, the third fluid may be added to thedroplet-dissolving region during and/or following introduction of theemulsion to the droplet-dissolving region.

A “region” may be a sub-system, a reactor, a pipe, a tube, a section(e.g., of a pipe or tube), a container, or a portion thereof, or acombination thereof. Multiple elements may collectively form a singleregion; for example, a tube outlet and a container disposed in flowcommunication with the tube outlet, may collectively form a region. Aportion of an element may form a region; for example, a section of pipemay form a region.

The solvent contained in droplets of first fluid is then dissolved intoa mixture of the second and third fluids, leaving the solid particlesbehind. As solvent leaves, the particles begin to assemble, eventuallyforming particle assemblies from all of the particles that wereinitially contained in the droplets.

The fluid phase of the droplet-dissolving region may be agitated tospeed up the dissolution of solvent into third fluid. Also, agitation ofthe droplet-dissolving region can help keep the emulsion dropletsdiscrete (not agglomerated) until the first fluid has fully diffusedinto the continuous phase (second fluid plus third fluid). Agitation maybe accomplished via stirring, shaking, rolling, sonication, or acombination thereof, for example. The time period for dissolution may befrom about 30 seconds to 10 minutes, for example.

Some methods utilize a device for assembling a plurality of particlesinto particle assemblies, the device comprising:

-   -   (a) a microfluidic droplet-generating region;    -   (b) a first inlet to the droplet-generating region, wherein the        first inlet is configured to feed a first fluid containing        particles and a solvent for the particles;    -   (c) a second inlet to the droplet-generating region, wherein the        second inlet is configured to feed a second fluid that is not        fully miscible with the first fluid;    -   (d) a droplet outlet from the droplet-generating region, wherein        the droplet outlet is configured to withdraw droplets of the        first fluid dispersed in the second fluid; and    -   (e) a droplet-dissolving region containing a third fluid that is        a co-solvent for the first and second fluids, wherein the        droplet-dissolving region is configured to receive the droplets        from the droplet outlet and to remove the solvent from the        droplets, thereby forming particle assemblies.

Certain methods utilize a continuous-flow microfluidic system asdepicted in FIG. 4 . FIG. 4 is a schematic diagram of a continuous-flowmicrofluidic system 400 (and a method) for assembling a plurality ofparticles into particle assemblies, in some embodiments. In adroplet-generating region, there is a first inlet 402 configured to feeda first fluid, a second inlet 403 configured to feed a second fluid, anda third inlet 404 also configured to feed the second fluid. Flowchannels for first and second fluids, and for droplets 408, arefabricated within a platform 401. Within the droplet-generating region,an emulsion of droplets of the first fluid in a continuous phase of thesecond fluid, is formed. There is a droplet outlet 405 from thedroplet-generating region, configured to continuously withdraw droplets408 and to convey them through a flow channel 406 to an inlet 407 of adroplet-dissolving region in which the emulsion and the third fluid 409are combined. The third fluid 409 surrounds dissolving droplets 408 anddissolves both the first and second fluids, since the third fluid is aco-solvent for the first and second fluids. The droplet-dissolvingregion is preferably agitated. The solvent contained in droplets 408 istransported out and into third fluid 409, as depicted by the outwardarrows in FIG. 4 , eventually resulting in at least one assembly ofparticles. The assemblies may be recovered from liquid mixture 409 suchas by filtering, centrifuging, drying, or other recovery steps.

A microfluidic droplet-generating region, when employed, may be selectedfrom a flow-focusing configuration, a T-junction configuration, adielectrophoresis droplet-generating configuration, or an electrowettingon dielectric (EWOD) configuration. This specification herebyincorporates by reference herein Teh et al., “Droplet Microfluidics” LabChip, 2008, 8, 198-220.

In a flow-focusing configuration, the dispersed and continuous phasesare forced through a narrow region in the microfluidic device. Symmetricshearing by the continuous phase on the dispersed phase enables morecontrolled and stable generation of droplets. Properties such as channelgeometry, flow rate, and viscosity all play important roles incontrolling droplet generation.

In a T-junction configuration, the inlet channel containing thedispersed phase perpendicularly intersects the main channel whichcontains the continuous phase. The two phases form an interface at thejunction, and as fluid flow continues, the tip of the dispersed phaseenters the main channel. The shear forces generated by the continuousphase and the subsequent pressure gradient cause the head of thedispersed phase to elongate into the main channel until the neck of thedispersed phase thins and eventually breaks the stream into a droplet.The sizes of the droplets can be changed by altering the fluid flowrates, the channel widths, or the relative viscosity between the twophases. T-Junctions are not limited to single inlets.

Dielectrophoresis can be used to generate uniform droplets by pullingthe droplets from a fluid reservoir. The fluid can be electricallyneutral, and the force exerted on the uncharged fluid is caused by anon-uniform electric field. The operation principle behinddielectrophoresis-driven droplet formation is based on the phenomenonthat polarizable fluids will be attracted to areas of higher electricfield intensity. Dielectrophoresis functions through the contribution ofthree main forces: a wetting force on the interfacial line between thedroplet, its surrounding medium, and the surface it contacts; a force onthe interface of the two fluids; and a body force due to pressuregradients in the fluid. The size and uniformity of the droplets dependon the magnitude and the frequency of the applied voltage. The dropletsdo not need to be in contact with a surface, but the droplets shouldinclude a liquid of higher dielectric permittivity than its surroundingfluid.

In an electrowetting on dielectric (EWOD) configuration, dropletgeneration relies on the fact that an electric field can change theinterfacial energy between a fluid and the surface it is in contactwith. Since interfacial energy directly affects the contact angle, anelectrical field can be used to reduce the contact angle and cause thefluid to wet the surface. In essence, the hydrophilicity of an area canbe temporarily increased around the fluid stream. EWOD devices can befabricated as either a one-plane or two-plane device. In a two-planedevice, the ground electrode is typically placed on the top layer withthe control electrodes on the bottom. Both layers include an insulatinglayer separating the droplets from the electrodes. Activation of theelectrodes initiates fluid wetting of the channel and the fluid quicklybegins to form a short liquid finger between the electrodes. Theelectrodes are then switched off, reverting the surface to beinghydrophobic. This causes the finger to break off from the reservoir, andform a droplet. The size of the droplet is dependent on the electricfield strength, frequency of the applied field, and width of the channelopening.

A microfluidic droplet-generating region, when employed, may be madeusing any standard microfluidic fabrication method. See, for example,Iliescu et al., “A practical guide for the fabrication of microfluidicdevices using glass and silicon” Biomicrofluidics 2012 Mar.; 6(1):016505-016505-16, which is hereby incorporated by reference herein.Molded polymers (e.g., polydimethylsiloxane, polymethylmethacrylate,polycarbonate, and/or cyclic olefin copolymers); wet-etched, dry-etched,and/or plasma-etched glass; wet-etched, dry-etched, and/or plasma-etchedsilicon; molded glass; laser-cut, patterned glass; micro-sandblastedglass, and other materials may be used to fabricate the microfluidicdroplet-generating region. Flow-focusing channels may be fabricatedusing various methods including soft lithography or the insertion ofcapillary sheathes into microdevices, for example.

The droplet-generating region may be made by additively manufacturing(e.g. via stereolithography) a sacrificial pattern for the fluidpassages, conformally coating the passages (e.g., with parylene) orinfiltrating with a bulk material, and then selectively removing thesacrificial pattern (e.g. by chemical etching, such as with NaOH). SeeRoper et al. “Scalable 3D Bicontinuous Fluid Networks: Polymer HeatExchangers Toward Artificial Organs”, Advanced Materials Volume 27,Issue 15, Pages 2479-2484 (2015), which is hereby incorporated byreference, for details on this technique to make microfluidic regions.

It is emphasized that the step of generating an emulsion containing adispersed phase of first-fluid droplets in the second fluid, is by nomeans limited to microfluidics droplet generation. Other techniques forgenerating an emulsion include, for example, vortex mixing, ultrasonicmixing, impeller mixing, microfluidizing, and porous-glass dropletgeneration.

As used in this specification, a “droplet-generating region” refers to aregion of space wherein method step(s) of generating an emulsion is(are) performed. Likewise, a “droplet-dissolving region” refers to aregion of space wherein method step(s) of dissolving the solvent fromthe droplets into a mixture of the second fluid and third fluid is (are)performed. The droplet-dissolving region is configured fordissolving-droplet assembly of particles, which is synonymous withshrinking-droplet assembly of nanoparticles. The droplet-dissolvingregion may also be referred to as a dissolution region. Note that thedroplet-dissolving region is not limited to the laminar flow regime.

In some embodiments, both the first fluid and second fluid enter adroplet-generating region as continuous phases. Within thedroplet-generating region, the first fluid is changed from a continuousphase to a dispersed phase (having a plurality of droplets), since thefirst and second fluids are not completely miscible. The second fluidtypically remains a continuous phase within the droplet-generatingregion. In certain embodiments, at least some of the second fluid formsa second dispersed phase in the droplet-generating region, the firstdispersed phase being that of the first fluid.

The droplet-generating region preferably generates droplets of thedispersed phase of the first fluid that are uniform in size. The averagedroplet size may be from about 1 micron to about 500 microns indiameter, for example, with a standard deviation of less than 50%, lessthan 25%, less than 10%, less than 5%, or less than 1% of the averagedroplet size. The droplet size needs to be large enough to containmultiple particles, such as at least 2, 5, 10, 50, 100, 500, 10³, 10⁴,10⁵, or 10⁶ particles per droplet. The concentration of particles istypically uniform throughout the first fluid. Therefore, each of thedroplets typically contains a similar number of particles, such as astandard deviation of less than 50%, less than 25%, less than 10%, lessthan 5%, or less than 1% of the average number of particles per droplet.

When step (d) is continuous or semi-continuous, the flow rate of thefirst fluid into the droplet-generating region may be selected fromabout 0.1 to about 100 microliters/min, such as from about 1 to about 10microliters/min, for example. The flow rate of the second fluid into thedroplet-generating region may be selected from about 1 to about 1000microliters/min, such as from about 10 to about 100 microliters/min. forexample. The flow rates of first and second fluids are preferably tunedto avoid droplet coalescence within the droplet-generating region orwithin a droplet-dissolving region. When droplet coalescence is aconcern, the flow rate of the first fluid should typically be lower thanthe flow rate of the second fluid, so that there are longer separationdistances between individual droplets. For example, in variousembodiments, the ratio of the volumetric flow rate of the first fluid tothe volumetric flow rate of the second fluid is less than 1:1, 1:2,1:10, 1:20, 1:50, or 1:100.

In certain embodiments, the method utilizes a filter to remove a portionof the particles contained in the first fluid, prior to or inconjunction with feeding the first fluid to the droplet-generatingregion. Filtering out some of the particles (but not all of theparticles) may be done to control particle size, to removepre-agglomerated particles, or for other reasons.

Additional fluids (besides first and second fluids) may be introduced tothe droplet-generating region. For example, the droplet-generatingregion may be configured to bring together multiple types of fluidsinside a single droplet. These multiple fluids may be mixed prior todroplet formation, after droplet formation, or both prior to and afterdroplet formation. In some embodiments, the first fluid contains theparticles and solvent, while an additional fluid contains apH-adjustment substance, such as an acid or a base. The additional fluidmay contain the same solvent as in the first fluid, a different solvent,or no solvent (e.g., the additional fluid may consist of thepH-adjustment substance).

The droplets that are generated in the droplet-generating region aretransported to the droplet-dissolving region. The droplet transport ispreferably via continuous flow (e.g., see FIG. 4 ), but mayalternatively be via intermittent flow, semi-continuous flow, or in abatch process. In a batch process, a number of droplets may be formed,collected, and then introduced into the droplet-dissolving region. Incertain embodiments, the droplet transport is achieved through the airor another gas to the droplet-dissolving region, driven by gravity or bygeneration of a mist using a pump, for example.

In the droplet-dissolving region, some or all of the droplets dissolveinto the third fluid. Preferably, all of the droplets dissolve into thethird fluid, which requires the total volume of all droplets to notexceed the volumetric solubility of the first fluid in the combinationof the second fluid and third fluid in the droplet-dissolving region.

The dissolution of droplets in the droplet-dissolving region may beaccomplished by diffusion, convection, or a combination thereof. In someembodiments, the droplet-dissolving region is configured for gentleagitation, such as with stirring, shaking, rolling, sonication, or acombination thereof. When agitation is employed, the degree of agitationshould be high enough to promote convection and dissolution, but not sohigh to shear the droplets into finer droplets, which would redistributethe particles and increase the assembly dispersity index in the finalassemblies.

In preferred embodiments, the droplets do not coalesce during the timeperiod for dissolution in the droplet-dissolving region. Avoidingcoalescence may be achieved by agitation, as noted above, and/or throughthe use of a surfactant. Dilution of the droplets may also be done tominimize coalescence.

In some embodiments, the method employs heating or cooling one or morefluids to adjust their solubility properties. For example, thedroplet-generating region and/or the droplet-dissolving region may be inthermal communication with a temperature-control component, which may bea cooler, a heater, or a unit (e.g., a heat exchanger) capable of eithercooling or heating. The temperature-control component allows fluids tobe cooled or heated to adjust their solubility. Multipletemperature-control components may be in thermal communication with morethan one region. As one example, an emulsion may be created at lowtemperature (via cooling) in the droplet-generating region, and then inthe droplet-dissolving region, heating is applied to tune thedissolution rate. In some embodiments, at least one of the first fluid,second fluid, and third fluid, preferably at least two of these fluids,and more preferably all of these fluids, are independently controlled byone or more temperature-control components. The temperatures of thefirst fluid, second fluid, and third fluid may be independentlycontrolled to be, for example, about 0° C., 5° C., 10° C., 15° C., 20°C., 25° C., 30° C., 35° C., 40° C., or higher. In some embodiments, thetemperatures of the first fluid and the second fluid are both controlledto be lower than the temperature of the third fluid.

There are a number of variations of the invention, some of which willnow be further described.

The first fluid may contain more than one type of particles. There maybe variations in the composition and/or size of particles in the firstfluid. In some embodiments, the particles are characterized by a bimodalsize distribution, i.e. there are both small particles and largeparticles present. For example, first particles smaller than about 100nanometers may be present, along with second particles larger than about10 microns, both in the first fluid. In some embodiments, core-shellassemblies of the smaller particles on the larger particles may result.In other embodiments, core-shell structures contain a shell of largerparticles around a core of smaller particles.

One or more of the particles may themselves be assemblies ofnanoparticles. For example, in certain methods, relatively large (e.g.,about 10 microns or larger in size) assemblies of first nanoparticlesmay be formed first. These assemblies may then be loaded along withunassembled second nanoparticles, potentially of a differentcomposition, into the first fluid. The method is repeated, thus forminga shell of second nanoparticles on a core of assembled firstnanoparticles. This method of assembly may be repeated to build upmultiple shells.

When two types of particles are present, the pH of the first fluid maybe adjusted such that the two types of particles have either oppositecharge or the same charge. For example, for a desired core-shellstructure, the core and shell materials may be adjusted with pH toexhibit opposite surface charges, thereby encouraging electrostaticattraction. Alternatively, the core and shell materials may be adjustedwith pH to exhibit surface charges of the same polarity, therebyinhibiting electrostatic assembly prior to droplet dissolution-drivenassembly. For simultaneous assembly of multiple types of materials, theparticles preferentially exhibit the same surface charges, or at leastpolarities, to encourage co-assembly and inhibit electrostatic assemblyprior to droplet dissolution-driven assembly.

In some variations, the droplets are physically confined during dropletdissolution, to generate non-spherical shapes. The third fluid may beadded to the emulsion of the first and second fluids, creating a mixturethat is placed between parallel plates or in a tube or series or tubes,for example. The dissolution occurs while confining the droplets in onedimension or in two dimensions. For example, the droplet-dissolvingregion may be configured to confine the droplets in one dimension, suchas with a parallel-plate geometry, to create elongated or cylindricalassemblies rather than spherical assemblies that are normally made fromunconfined droplets (e.g., see FIG. 2 ). In another example, thedroplet-dissolving region may be configured to confine the droplets intwo dimensions, such as with a tubular geometry, to create ellipsoid orbiconvex lens-shaped assemblies (e.g., see FIG. 3 ).

In certain embodiments, an assembly is a hybrid assembly of aninterspersed assembly and a core-shell assembly. For example, theassembly may contain a shell and a core that are different, wherein atleast one of the core or shell is itself an interspersed assembly. Ifboth the core and shell are interspersed assemblies, then thecompositions and/or physical structures of the core and shell differ insome way, so that they can be distinguished, in these certainembodiments. Also, it will be recognized that an assembly havecharacteristics of an interspersed assembly as well as a core-shellassembly, especially at certain ratios of particles sizes and phasevolumes (refer to the assembly heuristics earlier in thisspecification).

Some embodiments thus provide a core-shell assembly of nanoparticles,the core-shell assembly comprising a first phase containing firstnanoparticles and a second phase containing second nanoparticles,wherein the second phase forms a shell surrounding a core containing thefirst phase, and wherein the core itself is an interspersed assemblycomprising the first phase plus a third phase (interspersed with thefirst phase) containing third nanoparticles. The first nanoparticles arecompositionally different than the second nanoparticles. The thirdnanoparticles may be compositionally the same as the secondnanoparticles in the shell, or the third nanoparticles may becompositionally different than the second nanoparticles in the shell.The overall core-shell assembly may have a volume from 1 μm³ to 1 mm³, apacking fraction from 20% to 100%, and an average relative surfaceroughness less than 5%.

Some other embodiments thus provide a core-shell assembly ofnanoparticles, the core-shell assembly comprising a first phasecontaining first nanoparticles and a second phase containing secondnanoparticles, wherein the second phase is in a shell surrounding a coreof the first phase, and wherein the shell itself is an interspersedassembly comprising the second phase plus a third phase (interspersedwith the second phase) containing third nanoparticles. The firstnanoparticles are compositionally different than the secondnanoparticles. The third nanoparticles may be compositionally the sameas the first nanoparticles in the core, or the third nanoparticles maybe compositionally different than the first nanoparticles in the core.The overall core-shell assembly may have a volume from 1 μm³ to 1 mm³, apacking fraction from 20% to 100%, and an average relative surfaceroughness less than 5%.

Both the core and the shell of a core-shell assembly may themselves beinterspersed assemblies. Certain embodiments thus provide a core-shellassembly of nanoparticles, the core-shell assembly comprising a firstphase containing first nanoparticles and a second phase containingsecond nanoparticles, wherein the second phase is in a shell surroundinga core containing the first phase, wherein the core itself is aninterspersed core assembly comprising the first nanoparticles plus athird phase (interspersed with the first phase) containing thirdnanoparticles, and wherein the shell itself is an interspersed shellassembly comprising the second nanoparticles plus a fourth phase(interspersed with the second phase) containing fourth nanoparticles.The first nanoparticles are compositionally different than the secondnanoparticles. The third nanoparticles may be compositionally the sameas the second nanoparticles in the shell, or the third nanoparticles maybe compositionally different than the second nanoparticles in the shell.The fourth nanoparticles may be compositionally the same as the firstnanoparticles in the core, or the fourth nanoparticles may becompositionally different than the first nanoparticles in the core. Theoverall core-shell assembly may have a volume from 1 μm³ to 1 mm³, apacking fraction from 20% to 100%, and an average relative surfaceroughness less than 5%.

It will also be recognized by a person skilled in the art that aninterspersed assembly, such as that shown in FIG. 6 , can be thought ofas a material with many interfaces and therefore many cores in acontinuous or semi-continuous sea of shell material, within a singleassembly. In some embodiments, these assemblies are useful asalternating-index-of-refraction structures. For such structures, smallercores (e.g., SiO₂ cores that are less than 300 nanometers on average)provide more interfaces with the shell material (e.g., LiYF₄). Thesealternating-index-of-refraction structures enable frequency-tunable andfrequency-shifting retroreflectors, for example.

Structures with more sizes of particles are possible. For example, ifthere initially are three sizes and compositions of nanoparticles, thedifferent nanoparticles may be assembled into interspersed structures orcore—inner shell—outer shell structures.

Hierarchical structures may also be created. Interspersed or core/shellassemblies may be first created. Then, the assemblies may be thermallyfused or chemically fused, such as by using hydrazine-derived,multifunctional ligands to bind the particles together. The fusedassemblies may be introduced into an assembly process again, along withdispersed nanoparticles. This repeated assembly process may utilizeshrinking droplets or charge titration.

Some variations of the invention provide an assembly of nanoparticles,wherein the assembly has a volume from 1 μm³ to 1 mm³, a packingfraction from 20% to 100%, and/or an average relative surface roughnessless than 5%.

The “packing fraction” (or packing density) of an assembly is thefraction of the total assembly volume occupied by the particles in theassembly. In some embodiments, the assembly packing fraction is at least90%. In various embodiments, the assembly packing fraction is about 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,99%, or 100%. The packing fraction is 100% minus the void (volume)density, i.e., tighter packing means fewer voids, and conversely,lower-density packing means a greater density of voids (open space).

“Relative surface roughness” is defined as a ratio of the size of aprotrusion on the surface to the diameter of the assembly. The assemblydiameter may be the effective diameter, i.e. the cube root of the volumeof the assembly if the diameter is not well-defined. Preferably, therelative surface roughness is less than 10 particle diameters divided bythe assembly diameter, more preferably less than 3 particle diametersdivided by the assembly diameter, and most preferably less than 1particle diameter divided by the assembly diameter. The average relativesurface roughness accounts for variations in protrusion sizes, averagedacross the entire surface of the assembly. In preferred embodiments, theaverage relative surface roughness of the assembly is less than 5%,which may be characterized as a “smooth” assembly surface. In variousembodiments, the average relative surface roughness of the assembly isabout, or less than about, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1%.

The assembly may be spherical, approximately spherical, ornon-spherical. An “approximately spherical” assembly means that theassembly has a sphericity of at least 0.9, 0.91, 0.92, 0.93, 0.94, 0.95,0.96, 0.97, 0.98, or 0.99. Sphericity is the ratio of the surface areaof a sphere with the same volume as the given assembly to the surfacearea of the assembly. A perfect sphere has a sphericity of exactly 1,which is the maximum value of sphericity.

The assembly may be defined by an aspect ratio. The aspect ratio isdefined as the ratio of the maximum assembly dimension to the minimumassembly dimension. In various embodiments, the assembly has an aspectratio of about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, orgreater. When the assembly is a perfect sphere, the aspect ratio is 1.0.As another example, the assembly may be a biconvex ellipsoid with oneaxis at least 1.2 times another axis. As another example, the assemblymay be a cylinder with a length that is at least 2 times the diameter.

The assembly may have a volume from about 1 μm³ to about 1 mm³ (10⁹ μm³)for example. In some embodiments, an assembly has a volume from about 8μm³ to about 8×10⁶ μm³. When there are multiple assemblies, there may bea range of assembly volumes with the average assembly volume being fromabout 1 μm³ to about 1 mm³, for example.

When there are multiple assemblies in an overall structure, the assemblydispersity index of the plurality of particle assemblies may be lessthan 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, 0.02, or 0.01, including 0(perfecting monodisperse assemblies). In some preferred embodiments, theassembly dispersity index of the plurality of particle assemblies isless than 0.1.

If the particles of the assembly are asymmetric, the long axes ofindividual particles are preferably aligned in the same direction withrespect to one another in the arrays. “Aligned” means the long axis ofthe particles have a full width at half maximum angular distributionwith respect to the array alignment direction of at most ±20°, and morepreferably at most ±10°.

In some embodiments, the particles are packed together and touching ornear touching in an assembly array. The center-to-center distancebetween particles may be less than the width of two particles. Morepreferably, the center-to-center distance between particles may be lessthan the width of 1.5 nanoparticles.

In various embodiments, the assembly contains a material selected fromthe group consisting of metals, metal oxides, metal fluorides, metalsulfides, metal phosphides, semiconductors, ceramics, glasses, polymers,and combinations thereof.

The assembly is preferably free of organic ligands. That is, theassembly is preferably free of ligands containing carbon, such ashydrocarbon ligands. Carbon-containing impurities may be presentunintentionally within the assembly or on the assembly surface.

In some embodiments (such as fluoride-based nanoparticles), thenanoparticles may have inorganic ligands (e.g., tetrafluoroborate,thiocyanate, or hexafluorophosphate) or other organic-free, positivelyor negatively charged ligands or hydrophilic ligands on the surface tohelp keep them dispersed in water. When present, the ligands may beloosely bound such that a zeta potential response with pH is observed.

Note that organic groups (including organic ligands) may be present inthe fluid(s), which is distinct from the particles in bulk solution.Also, organic material (e.g., an organic polymer) may be containedwithin or on the particles, but preferably not as organic ligands. Insome embodiments, substantially no organic material is present on or inthe particles. “Substantially no organic material,” “free of organicligands,” and like terminology should be construed to recognize thatthere may be impurities or other species unintentionally present inthese material assemblies, which do not significantly impact theproperties of the material assemblies.

The assembly is preferably not disposed on a substrate. In this context,a “substrate” means an initial, stationary solid surface (e.g., aplatform) on which the particles deposit during the assembly method.Preferred embodiments do not utilize a substrate for the assembly. Notethat a previous layer of particles being assembled is not considered asubstrate. Also, an initial assembly onto which particles are assembledinto a core-shell assembly is also not considered a substrate, since theassembly is not stationary. In FIG. 2 , the flat plates, whilestationary, are not surfaces onto which particles deposit duringassembly—rather, the flat plates geometrically constrain the transportpaths of solvent being dissolved out of droplets. The flat plates aretherefore not substrates as defined herein.

In some embodiments, the assembly of particles into an assembly via amethod disclosed herein may be followed by charge-titration assembly ofnanoparticles, thus creating a core-shell structure. In these or otherembodiments, the assembly of particles into an assembly via a methoddisclosed herein may be preceded by charge-titration assembly ofnanoparticles, thus creating a core-shell structure. Charge-titrationassembly of nanoparticles is disclosed in commonly owned U.S. patentapplication Ser. No. 15/241,536, filed on Aug. 19, 2016, and commonlyowned U.S. patent application Ser. No. 16/011,834, filed on Jun. 19,2018, which are each hereby incorporated by reference herein.Charge-titrating assembly allows spatial and temporal control over thezeta potential of the particles to achieve alignment and organization ofparticles, without requiring organic ligands or a substrate.

Optionally, selective metal plating is performed on and/or inside eachassembly. Selective metal plating may alternatively, or additionally, beperformed on the particles prior to assembly. Selective metal platingmay be done with gold, silver, copper, nickel, aluminum, or acombination thereof, for example. Exemplary metal plating processesinclude, but are not limited to, electroless deposition, electroplating,metal evaporation, sputtering, metal organic chemical vapor deposition,or light-induced deposition.

By selecting the assembly components (particle compositions) andengineering the number of interfaces, light scattering may becontrolled. As examples, use of rare earth metals allows frequencyupshifting, while use of InP or PbSe quantum dots allows frequencydownshifting. In some embodiments, an assembly is configured as, orwithin, a frequency-selective retroreflective tag that directionallyreturns a wavelength for long-distance selective detection usingconventional optical components. Certain embodiments that employ quantumdots provide photoluminescence at a different wavelength. The assembliesdisclosed herein may provide an orders-of-magnitude larger signal thanexisting luminescent materials.

EXAMPLES Example 1: Assembly of Spherical Lead Sulfide (PbS) Particles

A first fluid is 20 microliters dimethyl sulfoxide (DMSO) containing 50mg/mL lead(II) sulfide (PbS) nanoparticles with thiocyanate (SCN⁻)ligands. The PbS nanoparticles have an approximate size range of 40 nmto 80 nm. The thiocyanate ligands are present on the PbS nanoparticlesat a concentration of about 20 wt %, sufficient to render the PbSnanoparticles soluble in the first fluid. A second fluid is 1 mL methyllaurate (CH₃(CH₂)₁₀CO₂CH₃). A third fluid is 0.8 mL 1-octanol (C₈H₁₈O).The first fluid and second fluid are vortex-mixed for 30 seconds. Thethird fluid is then added and vortex-mixed for 2 minutes.

FIG. 5 is a scanning electron microscopy (SEM) image of an illustrativePbS particle assembly fabricated in this Example. The scale bar of FIG.5 is 10 microns. FIG. 5 shows that the particle assembly is spherical.The particle assembly contains lead(II) sulfide nanoparticles.

The particle assembly diameter is estimated to be 11.5 μm. Therefore theparticle assembly volume is estimated to be 800 μm³ (8×10⁻⁷ mm³). Theparticle assembly packing fraction is estimated to be about 80%. Theaverage relative surface roughness of the particle assembly is estimatedto be about 4%. The particle assembly is not disposed on a substrate.

Assembly of PbS or other oxidation-sensitive nanoparticles (e.g. PbSe),or nanoparticles which are not highly hydrophilic (e.g. nanoparticleswith thiocyanate ligands), has not been heretofore possible usingdissolving-droplet methods.

Example 2: Semi-ordered Interspersed Assembly of SiO₂ and LiYF₄Nanoparticles in a 2:1 v:v Ratio

Silica (SiO₂) nanoparticles are provided, wherein the SiO₂ nanoparticlesare approximately spherical with an average diameter of 261 nm. Yttriumlithium fluoride (LiYF₄) nanoparticles are provided, wherein the LiYF₄nanoparticles are square bipyramidal particles that are 140 nm along thelong axis and 40-80 nm along the short axis.

60 mg SiO₂ is added to 1.2 mL deionized water. 1.2 mL LiYF₄ (50 mg/mL indimethyl sulfoxide, DMSO) is added to the SiO₂ solution and sonicatedfor 5 min. A 600 μL LiYF₄/SiO₂ mixture is added to a 30 mL 1-octanolsolution in a centrifugal tube. The following mixing profile is appliedin a digital vortexer: 2 min mixing at 3000 rpm, and 3 min mixing at2300 rpm. The assembly solution is left at room temperature for 18hours, and then the solution is centrifuged at 3000 rpm for 1 min. Thesupernatant is poured out, leaving the assemblies in the centrifugetube. The assemblies are dried in a 95° C. oven overnight. The result isa plurality of semi-ordered interspersed assemblies with SiO₂ (firstnanoparticles) each surrounded by LiYF₄ (second nanoparticles).

FIG. 6 is a SEM image (scale bar=2 microns) of a semi-orderedinterspersed assembly containing SiO₂ surrounded by LiYF₄. In FIG. 6 ,the larger particles are SiO₂, and the semi-continuous phase containssmaller particles of LiYF₄. In this semi-ordered interspersed assembly,there is an average separation distance between discrete SiO₂nanoparticles, filled by the LiYF₄ phase.

Example 3: Semi-ordered Interspersed Assembly of SiO₂ and TiO₂Nanoparticles in a 2:1 v:v Ratio

Silica (SiO₂) nanoparticles are provided, wherein the SiO₂ nanoparticlesare approximately spherical with an average diameter of 261 nm. Titaniumdioxide (TiO₂) nanoparticles are provided, wherein the TiO₂nanoparticles are approximately spherical with an average diameter of100 nm.

60 mg SiO₂ is added to 2.4 mL TiO₂ solution (25 mg/mL in H₂O). TheTiO₂/SiO₂ mixture is sonicated for 5 min. A 600 μL TiO₂/SiO₂ mixture isadded to a 30 mL 1-octanol solution in a centrifugal tube. The followingmixing profile is applied in a digital vortexer: 2 min mixing at 3000rpm, and 3 min mixing at 2300 rpm. The assembly solution is left at roomtemperature for 18 hours, and then centrifuged at 3000 rpm for 1 min.The supernatant is poured out, leaving the assemblies in the centrifugetube. The assemblies are dried in a 95° C. oven overnight. The result isa plurality of semi-ordered interspersed assemblies with SiO₂ (firstnanoparticles) each surrounded by TiO₂ (second nanoparticles).

FIG. 7 is a SEM image (scale bar=2 microns) of a semi-orderedinterspersed assembly containing SiO₂ surrounded by TiO₂. In FIG. 7 ,the larger particles are SiO₂, and the semi-continuous phase containssmaller particles of TiO₂. In this semi-ordered interspersed assembly,there is an average separation distance between discrete SiO₂nanoparticles, filled by the TiO₂ phase.

Example 4: Interspersed Assembly of SiO₂ and ZnO Nanoparticles in a 1:1v:v Ratio

Silica (SiO₂) nanoparticles are provided, wherein the SiO₂ nanoparticlesare approximately spherical with an average diameter of 261 nm. Zincoxide (ZnO) nanoparticles are provided, wherein the ZnO nanoparticlesare approximately spherical with diameter of 50-80 nanometers.

30 mg SiO₂ is added to 1.95 mL deionized water. 0.45 mL ZnO (200 mg/mLin H₂O) is added to the SiO₂ solution and is sonicated for 5 min. A 600μL ZnO/SiO₂ mixture is added to a 30 mL 1-octanol solution in acentrifugal tube. The following mixing profile is applied in a digitalvortexer: 2 min mixing at 3000 rpm, and 3 min mixing at 2300 rpm. Theassembly solution is left in room temperature for 18 hours, and thencentrifuged at 3000 rpm for 1 min. The supernatant is poured out,leaving the assemblies in the centrifuge tube. The assemblies are driedin a 95° C. oven overnight. The result is a plurality of interspersedassemblies with SiO₂ (first nanoparticles) each surrounded by ZnO(second nanoparticles).

FIG. 8 is a SEM image (scale bar=4 microns) of an interspersed assemblycontaining SiO₂ surrounded by ZnO. In FIG. 8 , the larger particles areSiO₂, and the semi-continuous phase contains smaller particles of ZnO.The overall assemblies were spherical.

Example 5: Interspersed Assembly of SiO₂ and TiO₂ Nanoparticles in a1:1.4 v:v Ratio

Silica (SiO₂) nanoparticles are provided, wherein the SiO₂ nanoparticlesare approximately spherical with an average diameter of 261 nm. Titaniumdioxide (TiO₂) nanoparticles are provided, wherein the TiO₂nanoparticles are approximately spherical with an average diameter of100 nm.

5 mg SiO₂ is added to 0.6 mL of a solution of amine-coated TiO₂particles (25 mg/mL in H₂O). The mixture solution is sonicated for 5min. A 600 μL TiO₂/SiO₂ mixture is added to a 30 mL 1-octanol solutionin a centrifugal tube. The following mixing profile is applied in thedigital vortexer: 2 min mixing at 3000 rpm, and 3 min mixing at 2300rpm. The assembly solution is left at room temperature for 18 hours, andthen centrifuged at 3000 rpm for 1 min. The supernatant is poured out,leaving the assemblies in a centrifuge tube. The assemblies are dried ina 95° C. oven overnight. The result is a plurality of interspersedassemblies with SiO₂ (first nanoparticles) each surrounded by TiO₂(second nanoparticles). Note that in these assemblies, the ratio of thevolume of SiO₂ to the volume of TiO₂ is 1/1.4=0.71.

FIG. 9 is a SEM image (scale bar=5 microns) of an interspersed assemblycontaining SiO₂ surrounded by TiO₂. In FIG. 9 , the larger particles areSiO₂, and the semi-continuous phase contains smaller particles of TiO₂.

Example 6: Core-Shell Assembly of SiO₂ and ZnO Nanoparticles in a 1:1.8v:v Ratio

Silica (SiO₂) nanoparticles are provided, wherein the SiO₂ nanoparticlesare approximately spherical with an average diameter of 261 nm. Zincoxide (ZnO) nanoparticles are provided, wherein the ZnO nanoparticlesare approximately spherical with diameter of 50-80 nanometers.

12 mg SiO₂ is added to 300 μL deionized water. 300 μL ZnO (200 mg/mL inH₂O) is added to the SiO₂ solution and sonicated for 5 min. A 600 μLZnO/SiO₂ mixture is added to a 30 mL 1-octanol solution in a centrifugaltube. The following mixing profile is applied in the digital vortexer: 2min mixing at 3000 rpm, and 3 min mixing at 2300 rpm. The assemblysolution is left at room temperature for 18 hours, and then centrifugedat 3000 rpm for 1 min. The supernatant is poured out, leaving theassemblies in centrifuge tube. The assemblies are dried in a 95° C. ovenovernight. The result is a plurality of core-shell assemblies with acore of SiO₂ (first nanoparticles) and a shell of ZnO (secondnanoparticles). Note that in these assemblies, the ratio of the volumeof SiO₂ to the volume of ZnO is 1/1.8=0.56.

FIG. 10 is a SEM image (scale bar=5 microns) of a core-shell assemblycontaining a core of primarily SiO₂ (right-hand side of image)surrounded by a shell of primarily TiO₂ (left-hand side of image).

As can be observed in FIG. 10 , the SiO₂ core contains small amounts ofTiO₂, and the TiO₂ shell contains small amounts of SiO₂. That is, in thecore of this core-shell assembly, the core has a finite ratio of firstnanoparticles (SiO₂) to second nanoparticles (TiO₂), and the shell has afinite ratio of second nanoparticles to first nanoparticles.

Example 7: Core-Shell Assembly of SiO₂ and TiO₂ Nanoparticles in a 1:2.9v:v Ratio

Silica (SiO₂) nanoparticles are provided, wherein the SiO₂ nanoparticlesare approximately spherical with an average diameter of 261 nm. Titaniumdioxide (TiO₂) nanoparticles are provided, wherein the TiO₂nanoparticles are approximately spherical with an average diameter of100 nm.

5 mg SiO₂ is added to 1 mL solution of amine-coated TiO₂ particles (25mg/mL in H₂O). The mixture solution is sonicated for 5 min. 1 mLTiO₂/SiO₂ mixture is added to a 30 mL 1-octanol solution in acentrifugal tube. The following mixing profile is applied in the digitalvortexer: 2 min mixing at 3000 rpm, and 3 min mixing at 2300 rpm. Theassembly solution is left at room temperature for 18 hours, and thencentrifuged at 3000 rpm for 1 min. The supernatant is poured out,leaving the assemblies in a centrifuge tube. The assemblies are dried ina 95° C. oven overnight. The result is a plurality of core-shellassemblies with a core of SiO₂ (first nanoparticles) and a shell of TiO₂(second nanoparticles). Note that in these assemblies, the ratio of thevolume of SiO₂ to the volume of TiO₂ is 1/2.9=0.34.

FIG. 11 is a SEM image (scale bar=5 microns) of a core-shell assemblycontaining a core of primarily SiO₂ (top of image) surrounded by a shellof primarily TiO₂ (bottom of image).

Examples 2 to 7 demonstrate that the structure of these assemblies isdetermined by the size ratio between the first and second nanoparticlesand by the ratio of the total volumes of each nanoparticle type.

Example 8: Core-Shell Assembly of SiO₂ and LiYF₄ Particles

In this example, a shrinking-droplet method as shown in FIG. 2 isemployed to create a core-shell assembly. The material for the core isSiO₂ spheres with average diameter of 7.75 microns. The material for theshell is LiYF₄ particles with average effective size of about 100nanometers.

FIG. 12 is a SEM image (scale bar=10 microns) of a core-shell assemblycontaining a core of primarily SiO₂ surrounded by a shell of primarilyLiYF₄. The data from scanning electron microscopy (SEM) is combined withenergy dispersive analysis of X-rays (EDAX) to determine the compositiondistribution of the assembly, providing evidence that the core isprimarily SiO₂ and the shell (exterior) is primarily LiYF₄nanoparticles. The assemblies are visually smooth, with a relativesurface roughness estimated to be significantly less than 1%.

Example 9: Assembly to Control Light Frequency and Scattering

In this example, a shrinking-droplet method as shown in FIG. 2 isemployed to create semi-ordered assemblies with discrete SiO₂nanoparticles and a semi-continuous phase of LiYF₄ nanoparticles. Theaverage particle size for the SiO₂ nanoparticles is 261 nm. The LiYF₄nanoparticles are 40 nm×40 nm×100 nm square bipyramids.

FIG. 13 is a SEM image (scale bar=50 microns) of a plurality ofspherical or approximately spherical assemblies that each have discreteSiO₂ nanoparticles and a semi-continuous phase of LiYF₄ nanoparticles.

FIG. 14 is a SEM image (scale bar=1 micron) of an individual assembly(one of the spheres of FIG. 13 ) showing discrete SiO₂ nanoparticles anda semi-continuous phase of LiYF₄ nanoparticles. As can be observed inFIG. 14 , there are many interfaces between SiO₂ phase and LiYF₄ phase.The structure of FIG. 14 can also be regarded as one in which there aremany core-shell substructures.

In this example, the SiO₂ and LiYF₄ form a semi-ordered assembly withmany interfaces due to the use of many small cores. This structure isuseful for controlling light frequency and scattering. For example,architecting these spherical assemblies in a supported sheet wouldenable frequency-tunable retroreflectors.

Example 10: Improved IR Scattering With a Core-Shell Assembly

This example utilizes LiYF₄ as a core material and TiO₂ as a shellmaterial for a core-shell assembly. A shrinking-droplet method as shownin FIG. 2 is employed to create approximately spherical core-shellassemblies, each having a core containing LiYF₄ and a shell containingTiO₂. The average particle size for the SiO₂ nanoparticles is 261 nm.The average particle size for the TiO₂ nanoparticles is 50-100 nm.

FIG. 15 is a SEM image (scale bar=10 microns) of approximately sphericalcore-shell assemblies with LiYF₄ (larger spheres) and TiO₂ (the primaryshell material shown in FIG. 15 ).

The index of refraction of TiO₂ is about 2.5, and the index ofrefraction of LiYF₄ is about 1.4. The difference in index of refractionbetween core and shell is therefore about 1.1. This example demonstratesa Bragg stack with Δn≈1, with scattering pre-assembled LiYF₄ cores andTiO₂ shells.

The IR diffuse reflectance of these core-shell assemblies is measured asabout 30%, compared to the IR diffuse reflectance of about 15% for TiO₂particles alone.

In this detailed description, reference has been made to multipleembodiments and to the accompanying drawings in which are shown by wayof illustration specific exemplary embodiments of the invention. Theseembodiments are described in sufficient detail to enable those skilledin the art to practice the invention, and it is to be understood thatmodifications to the various disclosed embodiments may be made by askilled artisan.

Where methods and steps described above indicate certain eventsoccurring in certain order, those of ordinary skill in the art willrecognize that the ordering of certain steps may be modified and thatsuch modifications are in accordance with the variations of theinvention. Additionally, certain steps may be performed concurrently ina parallel process when possible, as well as performed sequentially.

All publications, patents, and patent applications cited in thisspecification are herein incorporated by reference in their entirety asif each publication, patent, or patent application were specifically andindividually put forth herein.

The embodiments, variations, and figures described above should providean indication of the utility and versatility of the present invention.Other embodiments that do not provide all of the features and advantagesset forth herein may also be utilized, without departing from the spiritand scope of the present invention. Such modifications and variationsare considered to be within the scope of the invention defined by theclaims.

What is claimed is:
 1. An interspersed assembly of nanoparticlescomprising a first phase containing first nanoparticles with an averagefirst-nanoparticle diameter and a second phase containing secondnanoparticles with an average second-nanoparticle diameter, wherein saidsecond phase is interspersed with said first phase, wherein said firstnanoparticles are compositionally different than said secondnanoparticles, wherein said interspersed assembly has a volume from 1μm³ to 1 mm³, wherein said interspersed assembly has a packing fractionfrom 20% to 100%, and wherein said interspersed assembly has an averagerelative surface roughness less than 5%, wherein said average relativesurface roughness is defined as a ratio of size of a protrusion on asurface of said interspersed assembly to effective diameter of saidinterspersed assembly, averaged across the entire surface of saidinterspersed assembly.
 2. The interspersed assembly of claim 1, whereinthe ratio of the average first-nanoparticle diameter to the averagesecond-nanoparticles diameter is selected from about 1.1 to about 100.3. The interspersed assembly of claim 1, wherein the ratio of the volumeof said first phase to the volume of said second phase is selected fromabout 0.5 to about
 8. 4. The interspersed assembly of claim 1, whereinsaid interspersed assembly is a semi-ordered assembly comprisingdiscrete particles of said first phase, wherein said discrete particlesare surrounded by a continuous phase of said second phase, andoptionally wherein the average separation between said discreteparticles is about 20% to about 1000% of the average first-nanoparticlediameter.
 5. The interspersed assembly of claim 1, wherein said firstnanoparticles and said second nanoparticles each contain a materialindependently selected from the group consisting of metals, metaloxides, metal fluorides, metal sulfides, metal phosphides, ceramics,glasses, polymers, and combinations thereof.
 6. The interspersedassembly of claim 5, wherein said first nanoparticles contain SiO₂, andwherein said second nanoparticles contain TiO₂, ZnO, LiYF₄, or acombination thereof.
 7. The interspersed assembly of claim 1, whereinsaid first nanoparticles are non-spherical and/or said secondnanoparticles are non-spherical.
 8. The interspersed assembly of claim1, wherein said interspersed assembly is spherical or approximatelyspherical.
 9. The interspersed assembly of claim 1, wherein said packingfraction is at least 90%.
 10. The interspersed assembly of claim 1,wherein said average relative surface roughness is less than 1%.
 11. Theinterspersed assembly of claim 1, wherein said interspersed assembly isfree of organic ligands.
 12. The interspersed assembly of claim 1,wherein said interspersed assembly is not disposed on a substrate.
 13. Acore-shell assembly of nanoparticles comprising a first phase containingfirst nanoparticles with an average first-nanoparticle diameter and asecond phase containing second nanoparticles with an averagesecond-nanoparticle diameter, wherein said second phase forms a shellsurrounding a core of said first phase, wherein said first nanoparticlesare compositionally different than said second nanoparticles, whereinsaid core-shell assembly has a volume from 1 μm³ to 1 mm³, wherein saidcore-shell assembly has a packing fraction from 20% to 100%, and whereinsaid core-shell assembly has an average relative surface roughness lessthan 5%%, wherein said average relative surface roughness is defined asa ratio of size of a protrusion on a surface of said core-shell assemblyto effective diameter of said core-shell assembly, averaged across theentire surface of said core-shell assembly.
 14. The core-shell assemblyof claim 13, wherein the ratio of the average first-nanoparticlediameter to the average second-nanoparticles diameter is selected fromabout 1.1 to about
 100. 15. The core-shell assembly of claim 13, whereinthe ratio of the volume of said first phase to the volume of said secondphase is selected from about 0.1 to about 1.0.
 16. The core-shellassembly of claim 13, wherein said core contains a mass ratio of saidfirst nanoparticles to said second nanoparticles of at least
 5. 17. Thecore-shell assembly of claim 13, wherein said shell contains a massratio of said second nanoparticles to said first nanoparticles of atleast
 5. 18. The core-shell assembly of claim 13, wherein said firstnanoparticles and said second nanoparticles each contain a materialindependently selected from the group consisting of metals, metaloxides, metal fluorides, metal sulfides, metal phosphides, ceramics,glasses, polymers, and combinations thereof.
 19. The core-shell assemblyof claim 18, wherein said first nanoparticles contain SiO₂, and whereinsaid second nanoparticles contain TiO₂, ZnO, LiYF₄, or a combinationthereof.
 20. The core-shell assembly of claim 13, wherein said firstnanoparticles are non-spherical and/or said second nanoparticles arenon-spherical.
 21. The core-shell assembly of claim 13, wherein saidcore-shell assembly is spherical or approximately spherical.
 22. Thecore-shell assembly of claim 13, wherein said packing fraction is atleast 90%.
 23. The core-shell assembly of claim 13, wherein said averagerelative surface roughness is less than 1%.
 24. The core-shell assemblyof claim 13, wherein said core-shell assembly is free of organicligands.
 25. The core-shell assembly of claim 13, wherein saidcore-shell assembly is not disposed on a substrate.